Recruiting
Phase 1

LOXO-783

Sponsor:

Eli Lilly and Company

Code:

NCT05307705

Conditions

Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

LOXO-783

Fulvestrant

Imlunestrant

Abemaciclib

Anastrozole, Exemestane, or Letrozole

Study Details

Brief summary:

The main purpose of this study is to learn more about the safety, side effects, and effectiveness of LOXO-783. LOXO-783 may be used to treat breast cancer and other solid tumors that have a change in a particular gene (known as the PIK3CA gene). Participation could last up to 36 months (3 years) and possibly longer if the disease does not get worse.

Conditions

Breast Cancer

Study ID

NCT05307705

Start date

May 11, 2022

Status verified date

Sep, 2026

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Have advanced breast cancer or another solid tumor with the presence of a phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) H1047R mutation (or other Sponsor and safety review committee (SRC)-approved, activating PIK3CA mutations other than H1047R mutation)
  • Have adequate archival tumor tissue sample available or be approved by the Sponsor for enrollment if no tumor sample is available.
  • Have stopped all cancer treatment and have recovered from the major side effects
  • Have adequate organ function, as measured by blood tests
  • Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
  • Patients must have

  • Measurable disease

\--- Patients with non-breast tumor types must have at least 1 measurable lesion
  • Non-measurable bone disease (at least 1 bone lesion in breast cancer patients only)
  • For patients with an estrogen receptor (ER)+ breast cancer diagnosis:

  • If female, must be postmenopausal
  • If male, must agree to use hormone suppression
  • Phase 1a:

\-- Dose escalation and backfill patients:
  • Advanced solid tumor
  • Patients may have had up to 5 prior regimens for advanced disease
  • Phase 1b:

  • Part A:

  • ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer
  • Patients may have had up to 5 prior regimens for advanced disease ---- Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required
  • Part B:

  • ER+/HER2- advanced breast cancer
  • Patients may have had up to 2 prior regimens for advanced disease.
  • Part C:

  • ER+/HER2- advanced breast cancer
  • Patients may have had up to 5 prior regimens for advanced disease.

\---- Prior CDK4/6 inhibitor therapy required.
  • Have a diagnosis of diabetes mellitus Type 2
  • Part D:

  • Advanced breast cancer
  • Patients may have had up to 5 prior regimens for advanced disease.
  • Part E:

  • Advanced solid tumor
  • Patients may have had up to 3 prior regimens for advanced disease advanced disease
  • Part F:

  • ER+/HER2- advanced breast cancer
  • Patients may have had up to 5 prior regimens for advanced disease

  • Prior cyclin dependent kinase (CDK)4/6 inhibitor therapy required

Exclusion Criteria:

  • Medical Conditions

  • Colorectal cancer
  • Endometrial cancers with specific concurrent oncogenic alterations
  • A history of known active or suspected

  • Diabetes mellitus Type 1 or
  • Diabetes mellitus Type 2 requiring antidiabetic medication (Phase 1a and all parts of Phase 1b except Part C).
  • Serious concomitant systemic disorder
  • Known or suspected history of untreated or uncontrolled central nervous system (CNS) involvement.
  • Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection, or other clinically significant active disease process
  • Prior exposure to phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) inhibitor(s), except in certain circumstances

Study Design

Enrollment

260 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1A: LOXO-783 Monotherapy Dose Escalation

LOXO-783 administered orally

experimental: Phase 1B: Part A

LOXO-783 administered orally in combination with fulvestrant intramuscularly, imlunestrant orally, or an aromatase inhibitor orally

experimental: Phase 1B: Part B

LOXO-783 orally in combination with abemaciclib and either physician's choice aromatase inhibitor orally, fulvestrant intramuscularly, or imlunestrant orally

experimental: Phase 1B: Part C

LOXO-783 orally in combination with fulvestrant intramuscularly

experimental: Phase 1B: Part D

LOXO-783 orally in combination with paclitaxel intravenously

experimental: Phase 1B: Part E

LOXO-783 orally

experimental: Phase 1B: Part F

Multiple randomized dose levels of LOXO-783 orally with fulvestrant intramuscularly

Interventions

LOXO-783

Oral

Fulvestrant

Intramuscular

Imlunestrant

Oral

Abemaciclib

Oral

Anastrozole, Exemestane, or Letrozole

Oral

Paclitaxel

Intravenous

Primary outcome measure

  • Phase 1 a: To determine the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of LOXO-783: Number of patients with dose-limiting toxicities (DLTs) [ Time Frame: During the first 28-day cycle of LOXO-783 treatment ]
  • Phase 1 a: To determine the MTD/RP2D of LOXO-783: Number of patients with DLT-equivalent toxicities [ Time Frame: During the first 28-day cycle of LOXO-783 treatment ]

Central Contacts and Locations

Central contacts

There may be multiple sites in this clinical trial 1-877-CTLILLY (1-877-285-4559) or

13176154559ClinicalTrials.gov@lilly.com

Locations

UCSF Medical Center at Mission Bay

Recruiting

San Francisco, California, United States, 94158

Stanford University Hospital

Recruiting

Stanford, California, United States, 94305

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905-0002

UT Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390-8884

BC Cancer Vancouver

Recruiting

Vancouver, Canada, V5Z4E6

More Information

Sponsor

Eli Lilly and Company

Last update posted

Sep 8, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-09-08.